Edward M Schaeffer

Johns Hopkins University, Baltimore, Maryland, United States

Are you Edward M Schaeffer?

Claim your profile

Publications (100)384.32 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: To report race-based outcomes after radical prostatectomy (RP) in a cohort stratified by National Comprehensive Cancer Network (NCCN) risk category with updated follow-up. Studies describing racial disparities in outcomes after RP are conflicting. We studied 15,993 white and 1634 African American (AA) pretreatment-naïve men who underwent RP at our institution (1992-2013) with complete preoperative and pathologic data. Pathologic outcomes were compared between races using appropriate statistical tests; biochemical recurrence (BCR) for men with complete follow-up was compared using multivariate models that controlled separately for preoperative and postoperative covariates. Very low- and low-risk AA men were more likely to have positive surgical margins (P <.01), adverse pathologic features (P <.01), and be upgraded at RP (P <.01). With a median follow-up of 4.0 years after RP, AA race was an independent predictor of BCR among NCCN low-risk (HR, 2.16; P <.001) and intermediate-risk (hazard ratio [HR], 1.34; P = .024) classes and pathologic Gleason score ≤6 (HR, 2.42; P <.001) and Gleason score 7 (HR, 1.71; P <.001). BCR-free survival for very low-risk AA men was similar to low-risk white men (P = .890); BCR-free survival for low-risk AA men was similar to intermediate-risk white men (P = .060). When stratified by NCCN risk, AA men with very low-, low-, or intermediate-risk prostate cancer who undergo RP are more likely to have adverse pathologic findings and BCR compared with white men. AA men with "low risk" prostate cancer, especially those considering active surveillance, should be counseled that their recurrence risks can resemble those of whites in higher risk categories. Copyright © 2014 Elsevier Inc. All rights reserved.
    Urology 12/2014; 84(6):1434-41. · 2.42 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective To assess the association between magnetic resonance (MR) appearance of prostate cancer on a baseline multiparametric prostate (MP) MR imaging (MRI) and biopsy outcome in men with favorable-risk prostate cancer managed with active surveillance (AS). Materials and Methods Ninety-six consecutive men (mean age, 67.8 years) who had a baseline MP MRI within 1 year of AS enrollment were included in the study. MP MRI results were analyzed to identify men with MR-invisible tumor defined as no signal abnormality on T2-weighted images, no focal restricted diffusion, and no perfusion abnormality on dynamic contrast-enhanced images. Patients with (n = 84) or without (n = 12) MR-visible tumor were compared and the impact of MR-invisibility of tumor on the risk of adverse biopsy pathology based on the Epstein criteria was investigated with a median follow-up of 23 months. Results Adverse biopsy pathology occurred in 36.5% (35 of 96) of patients. There was no significant difference in the fulfillment of AS criteria at enrollment, prostate-specific antigen level or density, prostate volume, and number of biopsies (total or after MRI) between the 2 groups of patients. A total of 8.3% (1 of 12) of men with MR-invisible tumor had adverse biopsy pathology as compared with 40.5% (34 of 84) of men with MR-visible tumors. The MR-invisibility of tumor was associated with a lower risk of adverse biopsy pathology (crude relative risk = 0.35; 95% confidence interval, 0.10-1.25; prostate-specific antigen density–adjusted relative risk = 0.21; 95% confidence interval, 0.03-1.32). Conclusion The MR-invisibility of tumor on MP MRI could be of prognostic significance in monitoring men in AS with potential benefit of tailoring the frequency of surveillance biopsies and reducing the number of unnecessary biopsies.
    Urology 10/2014; · 2.42 Impact Factor
  • Debasish Sundi, Edward M Schaeffer
    Urology 10/2014; · 2.42 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND The use of multidisciplinary clinics (MDCs) for outpatient cancer evaluation is increasing. MDCs may vary in format, and data on whether MDCs change prostate cancer (PCa) care are limited. Here we report on the setup and design of a relatively new PCa MDC clinic. Because MDC evaluation was associated with a comprehensive re-evaluation of all patients' staging and risk stratification data, we studied the frequency of changes in PCa grade and stage upon MDC evaluation, which provides a unique estimate of the magnitude of pathology, radiology, and exam-based risk stratification in a modern tertiary setting.METHODS In 2008–2012, 887 patients underwent consultation for newly diagnosed PCa at the Johns Hopkins Hospital (JHH) weekly MDC. In a same-day process, patients are interviewed and examined in a morning clinic. Examination findings, radiology studies, and biopsy slides are then reviewed during a noon conference that involves real-time collaboration among JHH attending specialty physicians: urologists, radiation oncologists, medical oncologists, pathologists, and radiologists. During afternoon consultations, attending physicians appropriate to each patient's eligible treatment options individually meet with patients to discuss management strategies and/or clinical trials. Retrospective chart review identified presenting tumor characteristics based on outside assessment, which was compared with stage and grade as determined at MDC evaluation.RESULTSOverall, 186/647 (28.7%) had a change in their risk category or stage. For example, 2.9% of men were down-classified as very-low-risk, rendering them eligible for active surveillance. 5.7% of men thought to have localized cancer were up-classified as metastatic, thus prompting systemic management approaches. Using NCCN guidelines as a benchmark, many men were found to have undergone non-indicated imaging (bone scan 23.9%, CT/MRI 47.4%). The three most chosen treatments after MDC evaluation were external beam radiotherapy ± androgen deprivation (39.3%), radical prostatectomy (32.0%), and active surveillance/expectant management (12.9%).CONCLUSIONSA once-weekly same-day evaluation that involves simultaneous data evaluation, management discussion, and patient consultations from a multidisciplinary team of PCa specialists is feasible. Comprehensive evaluation at a tertiary referral center, as demonstrated in a modern MDC setting, is associated with critical changes in presenting disease classification in over one in four men. Prostate © 2014 Wiley Periodicals, Inc.
    The Prostate 10/2014; · 3.84 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Inflammation is associated with several diseases of the prostate including benign enlargement and cancer, but a causal relationship has not been established. Our objective was to characterize the prostate inflammatory microenvironment after infection with a human prostate derived bacterial strain and to determine the effect of inflammation on prostate cancer progression. To this end, we mimicked typical human prostate infection with retrograde urethral instillation of CP1, a human prostatic isolate of Escherichia coli. CP1 bacteria were tropic for the accessory sex glands and induced acute inflammation in the prostate and seminal vesicles with chronic inflammation lasting at least one year. Compared to controls, infection induced both acute and chronic inflammation with epithelial hyperplasia, stromal hyperplasia, and inflammatory cell infiltrates. In areas of inflammation, epithelial proliferation and hyperplasia often persist despite decreased expression of androgen receptor (AR). Inflammatory cells in the prostates of CP1 infected mice were characterized at 8 weeks post-infection by flow cytometry, which showed an increase in macrophages and lymphocytes, particularly Th17 cells. Inflammation was additionally assessed in the context of carcinogenesis. Multiplex cytokine profiles of inflamed prostates showed distinct inflammatory cytokines were expressed during prostate inflammation and cancer, with a subset of cytokines synergistically increased during concurrent inflammation and cancer. Furthermore, CP1 infection in the Hi-Myc mouse model of prostate cancer accelerated the development of invasive prostate adenocarcinoma with 70% more mice developing cancer by 4.5 months of age. This study provides direct evidence that prostate inflammation accelerates prostate cancer progression, and gives insight into the microenvironment changes induced by inflammation that may accelerate tumour initiation or progression.
    The Journal of Pathology 10/2014; · 7.59 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Rectal swabs can identify men with fluoroquinolone (FQ)-resistant bacteria and reduce rates of infection after transrectal ultrasound guided prostate biopsy (TRUSB) by targeted antimicrobial prophylaxis. We evaluated the rate of FQ resistance in an active surveillance cohort with attention to factors associated with resistance and changes in resistance over time.
    The Journal of urology 08/2014; · 3.75 Impact Factor
  • Source
    BJU International 04/2014; · 3.05 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective To evaluate the risk of reclassification on serial biopsy for Caucasian and African American (AA) men with very low-risk (VLR) prostate cancer enrolled in a large prospective active surveillance (AS) registry. Methods The Johns Hopkins AS registry is a prospective observational study that has enrolled 982 men since 1994. Including only men who met all National Comprehensive Cancer Network VLR criteria (clinical stage ≤T1, Gleason score ≤6, prostate-specific antigen [PSA] level <10 ng/mL, PSA density <0.15 ng/mL/cm3, positive cores <3, percent cancer per core ≤50), we analyzed a cohort of 654 men (615 Caucasians and 39 AAs). The association of race with reclassification on serial biopsy was assessed with competing-risks regressions. Results AA men on AS were more likely than Caucasians to experience upgrading on serial biopsy (36% vs 16%; adjusted P <.001). Adjusting for PSA level, prostate size, volume of cancer on biopsy, treatment year, and body mass index, AA race was an independent predictor of biopsy reclassification (subdistribution hazard ratio, 1.8; P = .003). Examining specific modes of reclassification, AA race was independently associated with reclassification by grade (subdistribution hazard ratio, 3.0; P = .002) but not by volume. Conclusion AA men with VLR prostate cancer followed on AS are at significantly higher risk of grade reclassification compared with Caucasians. Therefore, if the goal of AS is to selectively monitor men with low-grade disease, AA men may require alternate selection criteria.
    Urology 04/2014; · 2.42 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Purpose Of men with very low risk prostate cancer at biopsy recent evidence shows that black American men are at greater risk for adverse oncologic outcomes after radical prostatectomy. We studied radical prostatectomy specimens from black and white men at very low risk to determine whether there are systematic pathological differences. Materials and Methods Radical prostatectomy specimens were evaluated in men with National Comprehensive Cancer Network® (NCCN) very low risk prostate cancer. At diagnosis all men underwent extended biopsy sampling (10 or more cores) and were treated in the modern Gleason grade era. We analyzed tumor volume, grade and location in 87 black and 89 white men. For each specimen the dominant nodule was defined as the largest tumor with the highest grade. Results Compared to white men, black men were more likely to have significant prostate cancer (61% vs 29%), Gleason 7 or greater (37% vs 11%, each p <0.001) and a volume of greater than 0.5 cm3 (45% vs 21%, p = 0.001). Dominant nodules in black men were larger (median 0.28 vs 0.13 cm3, p = 0.002) and more often anterior (51% vs 29%, p = 0.003). In men who underwent pathological upgrading the dominant nodule was also more frequently anterior in black than in white men (59% vs 0%, p = 0.001). Conclusions Black men with very low risk prostate cancer at diagnosis have a significantly higher prevalence of anterior cancer foci that are of higher grade and larger volume. Enhanced imaging or anterior zone sampling may detect these significant anterior tumors, improving the outcome in black men considering active surveillance.
    The Journal of Urology. 01/2014; 191(1):60–67.
  • Debasish Sundi, Edward M Schaeffer
    Oncology (Williston Park, N.Y.) 01/2014; 28(1):83, 85. · 3.19 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Background:Outcomes in men with National Comprehensive Cancer Network (NCCN) high-risk prostate cancer (PCa) can vary substantially-some will have excellent cancer-specific survival, whereas others will experience early metastasis even after aggressive local treatments. Current nomograms, which yield continuous risk probabilities, do not separate high-risk PCa into distinct sub-strata. Here, we derive a binary definition of very-high-risk (VHR) localized PCa to aid in risk stratification at diagnosis and selection of therapy.Methods:We queried the Johns Hopkins radical prostatectomy database to identify 753 men with NCCN high-risk localized PCa (Gleason sum 8-10, PSA >20 ng ml(-1), or clinical stage T3). Twenty-eight alternate permutations of adverse grade, stage and cancer volume were compared by their hazard ratios for metastasis and cancer-specific mortality. VHR criteria with top-ranking hazard ratios were further evaluated by multivariable analyses and inclusion of a clinically meaningful proportion of the high-risk cohort.Results:The VHR cohort was best defined by primary pattern 5 present on biopsy, or 5 cores with Gleason sum 8-10, or multiple NCCN high-risk features. These criteria encompassed 15.1% of the NCCN high-risk cohort. Compared with other high-risk men, VHR men were at significantly higher risk for metastasis (hazard ratio 2.75) and cancer-specific mortality (hazard ratio 3.44) (P<0.001 for both). Among high-risk men, VHR men also had significantly worse 10-year metastasis-free survival (37% vs 78%) and cancer-specific survival (62% vs 90%).Conclusions:Men who meet VHR criteria form a subgroup within the current NCCN high-risk classification who have particularly poor oncological outcomes. Use of these characteristics to distinguish VHR localized PCa may help in counseling and selection optimal candidates for multimodal treatments or clinical trials.Prostate Cancer and Prostatic Disease advance online publication, 5 November 2013; doi:10.1038/pcan.2013.46.
    Prostate Cancer and Prostatic Diseases 11/2013; · 2.81 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background:Due to their varied outcomes, men with biochemical recurrence (BCR) following radical prostatectomy (RP) present a management dilemma. Here, we evaluate Decipher, a genomic classifier (GC), for its ability to predict metastasis following BCR.Methods:The study population included 85 clinically high-risk patients who developed BCR after RP. Time-dependent receiver operating characteristic (ROC) curves, weighted Cox proportional hazard models and decision curves were used to compare GC scores to Gleason score (GS), PSA doubling time (PSAdT), time to BCR (ttBCR), the Stephenson nomogram and CAPRA-S for predicting metastatic disease progression. All tests were two-sided with a type I error probability of 5%.Results:GC scores stratified men with BCR into those who would or would not develop metastasis (8% of patients with low versus 40% with high scores developed metastasis, P<0.001). The area under the curve for predicting metastasis after BCR was 0.82 (95% CI, 0.76-0.86) for GC, compared to GS 0.64 (0.58-0.70), PSAdT 0.69 (0.61-0.77) and ttBCR 0.52 (0.46-0.59). Decision curve analysis showed that GC scores had a higher overall net benefit compared to models based solely on clinicopathologic features. In multivariable modeling with clinicopathologic variables, GC score was the only significant predictor of metastasis (P=0.003).Conclusions:When compared to clinicopathologic variables, GC better predicted metastatic progression among this cohort of men with BCR following RP. While confirmatory studies are needed, these results suggest that use of GC may allow for better selection of men requiring earlier initiation of treatment at the time of BCR.Prostate Cancer and Prostatic Disease advance online publication, 22 October 2013; doi:10.1038/pcan.2013.49.
    Prostate cancer and prostatic diseases 10/2013; · 2.10 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We report the 30-year institutional experience of radical prostatectomy (RP) for men with clinically localized prostate cancer (PC) found to have lymph node (LN) metastases at surgery. The Johns Hopkins RP Database (1982-2011) was queried for 505 (2.5%) men with node-positive (N1) PC. Survival analysis was completed using the Kaplan-Meier method and proportional hazard regression models. The proportion of men with N1PC was 8.3%, 3.5%, and 1.4% in the pre- (1982-1990), early- (1991-2000), and contemporary-PSA eras (2001-2011), respectively. A trend toward decreasing PSA, less palpable disease but more advanced Gleason sum was noted in the most contemporary era. Median total and positive nodes were 13.2 (1-41) and 1.7 (1-12), respectively. Of 135 patients with a unilateral tumor, 80 (59.3%), 28 (20.7%), and 15 (11.1%) had ipsilateral, contralateral, and bilateral positive LN. 15-year biochemical-recurrence free, metastases-free and cancer-specific survival was 7.1%, 41.5%, and 57.5%, respectively. Predictors of biochemical-recurrence, metastases and death from PC in multivariate analysis included Gleason sum at RP, the number and percent of positive LN; notably total number of LN dissected did not predict outcome. In this highly-selected RP cohort, men found to have N1PC disease at RP can experience a durable long-term metastases-free and cancer-specific survival. Predictors of survival include Gleason sum, number, and percentage of positive LN. While total number of LN dissected was not predictive, approximately 30% of men with N1PC will have positive LN contralateral to the primary prostatic lesion highlighting the importance of a thorough, bilateral pelvic LN dissection. Prostate © 2013 Wiley Periodicals, Inc.
    The Prostate 09/2013; · 3.84 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Standard clinical care pathways to discharge have been established for a number of operations including radical prostatectomy (RP). The pathway after RP has changed dramatically over the past two decades due to improvements in surgical technique, anaesthesia and most recently, the introduction of minimally invasive RP (MIRP). This study adds evidence that the emergence of MIRP is associated with a decrease in LOS for all patients undergoing RP. In addition, it catalogues the development of the clinical care pathway over 20 years at a large, tertiary care hospital with extensive experience in RP. Finally, it defines the common reasons patients fall 'off-pathway' (ileus, urine leak, anaemia and re-exploration for bleeding) and defines the immediate perioperative morbidity profile of RP. Specifically, it addresses approach-specific morbidities and indicates that MIRP is associated with higher rates of 'off-pathway' discharge, most often due to ileus. To investigate the development of the clinical care pathway to discharge after radical prostatectomy (RP) at a large, academic medical centre over the past 20 years, focusing on the rates and reasons for deviation. In all, 18 049 men were identified from the Johns Hopkins RP database who had undergone surgery since 1991. Patients in whom the length of stay (LOS) was ≤95th percentile, defined the clinical care pathway to discharge and those in whom LOS was ≥98th percentile were termed 'off-pathway'. The mean LOS decreased from 7.7 days in 1991 to 1.6 days in 2010. Of 7126 patients undergoing RP since 2005, 1803(25.3%), 4881(68.5%) and 312 (4.4%) were discharged on postoperative day (POD) 1, 2 and 3, respectively; 126 (1.8%) patients, discharged on POD4-21 were 'off-pathway'. The most common reasons for delay of discharge were ileus (44, 0.615%), urine leak (12, 0.17%), anaemia requiring blood transfusion (nine, 0.126%) and bleeding requiring re-exploration (six, 0.08%). The proportion of patients 'off-pathway' was 1.20%, 1.06% and 4.01% for retropubic RP (RRP), laparoscopic RP (LRP) and robot-assisted laparoscopic RP (RALRP), respectively (P < 0.001). Ileus delayed discharge in 0.28%, 0.37% and 1.9% of patients undergoing RRP, LRP and RALRP, respectively (P < 0.001). The clinical care pathway to discharge after RP has changed dramatically at our institution over the past 20 years. RALRP appears to result in a higher proportion of 'off-pathway' patients, primarily due to ileus, compared with RRP and LRP. However, very few patients were discharged 'off-pathway'.
    BJU International 07/2013; 112(1):45-53. · 3.05 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSEActive surveillance (AS) is a treatment option for men with very low-risk prostate cancer (PCa); however, favorable outcomes achieved for men in AS are based on cohorts that under-represent African American (AA) men. To explore whether race-based health disparities exist among men with very low-risk PCa, we evaluated oncologic outcomes of AA men with very low-risk PCa who were candidates for AS but elected to undergo radical prostatectomy (RP). PATIENTS AND METHODS We studied 1,801 men (256 AA, 1,473 white men, and 72 others) who met National Comprehensive Cancer Network criteria for very low-risk PCa and underwent RP. Presenting characteristics, pathologic data, and cancer recurrence were compared among the groups. Multivariable modeling was performed to assess the association of race with upgrading and adverse pathologic features.ResultsAA men with very low-risk PCa had more adverse pathologic features at RP and poorer oncologic outcomes. AA men were more likely to experience disease upgrading at prostatectomy (27.3% v 14.4%; P < .001), positive surgical margins (9.8% v 5.9%; P = .02), and higher Cancer of the Prostate Risk Assessment Post-Surgical scoring system (CAPRA-S) scores. On multivariable analysis, AA race was an independent predictor of adverse pathologic features (odds ratio, [OR], 3.23; P = .03) and pathologic upgrading (OR, 2.26; P = .03). CONCLUSIONAA men with very low-risk PCa who meet criteria for AS but undergo immediate surgery experience significantly higher rates of upgrading and adverse pathology than do white men and men of other races. AA men with very low-risk PCa should be counseled about increased oncologic risk when deciding among their disease management options.
    Journal of Clinical Oncology 06/2013; · 18.04 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: INTRODUCTION: Among men with very-low-risk prostate cancer (PCa) at biopsy, recent evidence has shown that African American men (AA) are at greater risk for adverse oncologic outcomes after radical prostatectomy (RP). We studied RP specimens from very-low-risk AA and Caucasian men to determine if there were systematic pathological differences. MATERIALS AND METHODS: RP specimens were evaluated for men with National Comprehensive Cancer Network (NCCN) very-low-risk PCa. All men underwent extended biopsy sampling at diagnosis (≥10 cores) and were treated in the modern Gleason grading era. Tumor volumes, grades, and locations in 87 AA and 89 Caucasians were analyzed. For each specimen, the dominant nodule was defined as the largest tumor with highest grade. RESULTS: Compared to Caucasians, AA men were more likely to have significant PCa (61% vs 29%, p<0.001); Gleason ≥7 (37% vs 11%, p<0.001) and volume >0.5cm(3) (45% vs 21%, p=0.001). Dominant nodules in AA men were larger (median 0.28 cm(3) vs 0.13 cm(3), p=0.002) and more often anterior (51% vs 29%, p=0.003). Among men who underwent pathologic upgrading, the dominant nodule was also anterior more frequently in AA than in Caucasians (59% vs 0%, p=0.001). CONCLUSIONS: AA men with very-low-risk PCa at diagnosis have a significantly higher prevalence of anteriorly-located cancer foci that are of higher grade and larger volume. Enhanced imaging or anterior zone sampling may detect these significant, anterior tumors, thereby improving outcomes of AA men considering active surveillance.
    The Journal of urology 06/2013; · 3.75 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Outcomes for poor-risk localized prostate cancers treated with radiation are still insufficient. Targeting the "non-oncogene" addiction or stress response machinery is an appealing strategy for cancer therapeutics. Heat-shock-protein-90 (Hsp90), an integral member of this machinery, is a molecular chaperone required for energy-driven stabilization and selective degradation of misfolded "client" proteins that is commonly overexpressed in tumor cells. Hsp90 client proteins include critical components of pathways implicated in prostate cancer cell survival and radioresistance, such as androgen receptor signaling and the PI3K-Akt-mTOR pathway. We examined the effects of a novel non-geldanamycin Hsp90 inhibitor, AUY922, combined with radiation (RT) on two prostate cancer cell lines, Myc-CaP and PC3, using in vitro assays for clonogenic survival, apoptosis, cell cycle distribution, γ-H2AX foci kinetics and client protein expression in pathways important for prostate cancer survival and radioresistance. We then evaluated tumor growth delay and effects of the combined treatment (RT-AUY922) on the PI3K-Akt-mTOR and AR pathways in a hind-flank tumor graft model. We observed that AUY922 caused supra-additive radiosensitization in both cell lines at low nanomolar doses with enhancement ratios between 1.4-1.7 (p < 0.01). RT-AUY922 increased apoptotic cell death compared with either therapy alone, induced G 2-M arrest and produced marked changes in client protein expression. These results were confirmed in vivo, where RT-AUY922 combination therapy produced supra-additive tumor growth delay compared with either therapy by itself in Myc-CaP and PC3 tumor grafts (both p < 0.0001). Our data suggest that combined RT-AUY922 therapy exhibits promising activity against prostate cancer cells, which should be investigated in clinical studies.
    Cancer biology & therapy 01/2013; 14(4). · 3.29 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The ideal treatment for men with high-risk prostate cancer is controversial, although most physicians agree that a multimodal approach, including radiation and hormone therapy with or without surgery, offers the best chance of cancer control. Minimally-invasive radical prostatectomy has emerged as a treatment option for clinically localized cancer; however, critics argue that the open approach may afford advantages of tactile feedback and a better lymph node dissection. The present study demonstrates that open and minimally-invasive radical prostatectomy offer equivalent short-term outcomes for men with high-risk prostate cancer at a highly experienced centre. OBJECTIVES: To analyze pathological and short-term oncological outcomes in men undergoing open and minimally-invasive radical prostatectomy (MIRP) for high-risk prostate cancer (HRPC; prostate-specific antigen level [PSA] >20 ng/mL, ≥ cT2c, Gleason score 8-10) in a contemporaneous series. PATIENTS AND METHODS: In total, 913 patients with HRPC were identified in the Johns Hopkins Radical Prostatectomy Database subsequent to the inception of MIRP at this institution (2002-2011) Of these, 743 (81.4%) underwent open radical retropubic prostatectomy (ORRP), 105 (11.5%) underwent robot-assisted laparoscopic radical prostatectomy (RALRP) and 65 (7.1%) underwent laparoscopic radical prostatectomy (LRP) for HRPC. Appropriate comparative tests were used to evaluate patient and prostate cancer characteristics. Proportional hazards regression models were used to predict biochemical recurrence. RESULTS: Age, race, body mass index, preoperative PSA level, clinical stage, number of positive cores and Gleason score at final pathology were similar between ORRP and MIRP. On average, men undergoing MIRP had smaller prostates and more organ-confined (pT2) disease (P = 0.02). The number of surgeons and surgeon experience were greatest for the ORRP cohort. Overall surgical margin rate was 29.4%, 34.3% and 27.7% (P = 0.52) and 1.9%, 2.9% and 6.2% (P = 0.39) for pT2 disease in men undergoing ORRP, RALRP and LRP, respectively. Biochemical recurrence-free survival among ORRP, RALRP and LRP was 56.3%, 67.8% and 41.1%, respectively, at 3 years (P = 0.6) and the approach employed did not predict biochemical recurrence in regression models. CONCLUSIONS: At an experienced centre, MIRP is comparable to open radical prostatectomy for HRPC with respect to surgical margin status and biochemical recurrence.
    BJU International 01/2013; · 3.05 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSE: Among Medicare participants, we recently reported an increasing risk over time of hospitalization following an initial prostate biopsy. Less is known about the relative risks of repeat prostate biopsies, which are frequently performed in prostate cancer screening and in active surveillance programs. Our goal was to determine whether repeat biopsies are associated with an increased risk of hospitalization compared to initial biopsy. MATERIALS AND METHODS: Using Surveillance, Epidemiology and End Results (SEER)-linked Medicare data from 1991 to 2007, we identified 13,883 men who underwent a single prostate biopsy and 3640 with multiple biopsies. 30-day hospitalization rates were compared between these groups, and with a randomly selected control population (n=134,977). ICD-9 codes were then used to examine the frequency of serious infectious and non-infectious urological complications as the primary diagnosis for admissions. RESULTS: Both initial and repeat biopsies were associated with a significantly increased risk of hospitalization within a 30 day period compared to randomly selected controls (p<0.0001). However, the repeat biopsy session was not associated with a greater risk of infectious (OR 0.81, 95% 0.49-1.32, p=0.39) or serious non-infectious urological complications (OR 0.94, 95% CI 0.54-1.62, p=0.82) compared to the initial biopsy procedure. CONCLUSIONS: Each biopsy procedure is associated with significant risk of complications compared to randomly selected controls. However, the repeat biopsy procedure itself was not associated with a greater risk of serious complications requiring hospital admission compared to the initial biopsy.
    The Journal of urology 10/2012; · 3.75 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Prostate cancer is the second leading cause of cancer death among United States men. However, disease aggressiveness is varied, with low-grade disease often being indolent and high-grade cancer accounting for the greatest density of deaths. Outcomes are also disparate among men with high-grade prostate cancer, with upwards of 65% having disease recurrence even after primary treatment. Identification of men at risk for recurrence and elucidation of the molecular processes that drive their disease is paramount, as these men are the most likely to benefit from multimodal therapy. We previously showed that androgen-induced expression profiles in prostate development are reactivated in aggressive prostate cancers. Herein, we report the down-regulation of one such gene, Sparcl1, a secreted protein, acidic and rich in cysteine (SPARC) family matricellular protein, during invasive phases of prostate development and regeneration. We further demonstrate a parallel process in prostate cancer, with decreased expression of SPARCL1 in high-grade/metastatic prostate cancer. Mechanistically, we demonstrate that SPARCL1 loss increases the migratory and invasive properties of prostate cancer cells through Ras homolog gene family, member C (RHOC), a known mediator of metastatic progression. By using models incorporating clinicopathologic parameters to predict prostate cancer recurrence after treatment, we show that SPARCL1 loss is a significant, independent prognostic marker of disease progression. Thus, SPARCL1 is a potent regulator of cell migration/invasion and its loss is independently associated with prostate cancer recurrence.
    Proceedings of the National Academy of Sciences 09/2012; 109(37):14977-14982. · 9.81 Impact Factor

Publication Stats

860 Citations
384.32 Total Impact Points

Institutions

  • 2008–2014
    • Johns Hopkins University
      • • Department of Pathology
      • • Department of Medicine
      Baltimore, Maryland, United States
  • 2003–2014
    • Johns Hopkins Medicine
      • Department of Urology
      Baltimore, Maryland, United States
  • 2012
    • CUNY Graduate Center
      New York City, New York, United States
  • 2010
    • Northwestern University
      • Department of Urology
      Evanston, IL, United States